Liposome engraftment and antigen combination potentiate the immune response towards conserved epitopes of the malaria vaccine candidate MSP2

Vaccine. 2021 Mar 19;39(12):1746-1757. doi: 10.1016/j.vaccine.2021.02.010. Epub 2021 Feb 20.


Merozoite surface protein 2 (MSP2) is a highly abundant, GPI-anchored surface antigen on merozoites of the malaria parasite Plasmodium falciparum. It consists of highly conserved N- and C-terminal domains, and a central polymorphic region that allows all MSP2 alleles to be categorized into the 3D7 or FC27 family. Previously it has been shown that epitope accessibility differs between lipid-bound and lipid-free MSP2, suggesting that lipid interactions modulate the conformation and antigenicity in a way that may better mimic native MSP2 on the merozoite surface. Therefore, we have immunised mice with MSP2 engrafted onto liposomes using a C-terminal tether that mimics the native GPI anchor. To improve the immunogenicity of the formulated antigen, liposomes were supplemented with Pathogen Associated Molecular Pattern molecules, specifically agonists of the Toll-like receptor 4 (TLR4) or TLR2. Induced antibodies were directed mostly towards conserved epitopes, predominantly in the conserved C-terminal region of MSP2. We also found that immunisation with a combination of 3D7 and FC27 MSP2 enhanced antibody responses to conserved epitopes, and that the overall responses of mice immunised with MSP2-engrafted liposomes were comparable in magnitude to those of mice immunised with MSP2 formulated in Montanide ISA720. The antibodies elicited in mice by immunising with MSP2-engrafted liposomes recognised the native form of parasite MSP2 on western blots and were found to be cross-reactive with isolated 3D7 and FC27 merozoites when investigated by ELISA. The liposome-tethered MSP2 induced higher titres of complement-fixing antibodies to 3D7 and FC27 MSP2 than did MSP2 formulated in Montanide ISA720. Our results indicate that liposomal formulation represents a viable strategy for eliciting a strong immune response that favours conserved epitopes in MSP2 and thus a strain-transcendent immune response.

Keywords: Complement fixation; Conserved epitope; Immune response; Liposome; Malaria; Merozoite surface protein 2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Protozoan
  • Antigens, Protozoan / genetics
  • Epitopes
  • Immunity
  • Liposomes
  • Malaria Vaccines*
  • Malaria, Falciparum* / prevention & control
  • Membrane Proteins
  • Merozoites
  • Mice
  • Plasmodium falciparum
  • Protozoan Proteins / genetics


  • Antibodies, Protozoan
  • Antigens, Protozoan
  • Epitopes
  • Liposomes
  • Malaria Vaccines
  • Membrane Proteins
  • Protozoan Proteins